Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways

Biol Chem. 2022 Aug 10;403(10):929-943. doi: 10.1515/hsz-2022-0148. Print 2022 Sep 27.

Abstract

Osteosarcoma (OS) is the most prevalent malignant bone tumor with poor prognosis. Developing new drugs for the chemotherapy of OS has been a focal point and a major obstacle of OS treatment. Nitazoxanide (NTZ), a conventional anti-parasitic agent, has got increasingly noticed because of its favorable antitumor potential. Herein, we investigated the effect of NTZ on human OS cells in vitro and in vivo. The results obtained in vitro showed that NTZ inhibited the proliferation, migration and invasion, arrested cell cycle at G1 phase, while induced apoptosis of OS cells. Mechanistically, NTZ suppressed the activity of AKT/mTOR and Wnt/β-catenin signaling pathways of OS cells. Consistent with the results in vitro, orthotopic implantation model of 143B OS cells further confirmed that NTZ inhibited OS cells growth and lung metastasis in vivo. Notably, NTZ caused no apparent damage to normal cells/tissues. In conclusion, NTZ may inhibit tumor growth and metastasis of human OS cells through suppressing AKT/mTOR and Wnt/β-catenin signaling pathways.

Keywords: apoptosis; metastasis; osteosarcoma; proliferation; signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / metabolism
  • Bone Neoplasms* / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Nitro Compounds
  • Osteosarcoma* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • TOR Serine-Threonine Kinases / pharmacology
  • TOR Serine-Threonine Kinases / therapeutic use
  • Thiazoles
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • Nitro Compounds
  • Thiazoles
  • beta Catenin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • nitazoxanide